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Methicillin-Resistant Staphylococcus aureus (MRSA)

BASIC INFORMATION

SYNONYMS
Multidrug-resistant Staphylococcus aureus
Oxacillin-resistant Staphylococcus aureus
ICD-9CM CODES
041.12Methicillin-resistant Staphylococcus
aureus in conditions classified
elsewhere and of unspecified site
ICD-10CM CODES
B95.62Methicillin-resistant Staphylococcus
aureus infection as the cause of
diseases classified elsewhere

EPIDEMIOLOGY &
DEMOGRAPHICS
INCIDENCE: 1:3000
PEAK INCIDENCE: Occurs year round; may peak
during summer and fall months for CA-MRSA
PREVALENCE: The national rate of MRSA colonization or infection is 46.3 per 10,000 inpatients. Hospital prevalence rate of MRSA is as
high as 60% in hospitals, which means that
60% of S. aureus strains in that hospital will
be MRSA.
PREDOMINANT SEX AND AGE: All ages and
both sexes
GENETICS: NA
RISK FACTORS:
HA-MRSA: hospitalization; invasive medical
device; residing in long-term nursing facility


CA-MRSA: initially seen in young men
engaged in athletic activities and in gyms,
prisons, military barracks, etc., but has now
spread to the entire age spectrum including
neonates and the elderly.
PHYSICAL FINDINGS & CLINICAL
PRESENTATION
CA-MRSA: can present with skin infection,
associated with opening in the skin; red
bump, pustule, or boil; erythema, swelling;
edema, often fluctuant and very painful
HA-MRSA: bacteremia; infection associated
with intravenous device
1. Catheters: pneumonia
2. Skin: cellulitis
3. Bone: osteomyelitis
4. Endocarditis
5. Abscesses: skin or organ
6. Pneumonia: nosocomial

DIAGNOSIS
DIFFERENTIAL DIAGNOSIS
Skin: spider bite (many patients with CA-MRSA
feel as if they were bitten by a spider)
Cellulitis: other organism(s) such as streptococci and methicillin-sensitive S. aureus (MSSA)
Pneumonia: not due to MRSA
Bacteria: not due to MRSA
WORKUP

Culture of wound, abscess, blood, sputum;
rule out colonization; culture of nares or axillae
LABORATORY TESTS
See above.
PFGE: usually done only for epidemiologic or
outbreak purposes.
IMAGING STUDIES
Radiographs or computed tomography scan
of suspected organ


Echocardiogram: all adult patients with
S. aureus bacteremia should undergo
echocardiography

TREATMENT
CA-MRSA: oral antibiotics that may be effective include trimethoprim-sulfamethoxazole,
doxycycline, minocycline, or clindamycin;
linezolid is another option but very expensive.
HA-MRSA: intravenous antibiotics, vancomycin, linezolid, daptomycin, tigecycline

NONPHARMACOLOGIC THERAPY
Abscess surgically drained
ACUTE GENERAL Rx


Trimethoprim-sulfamethoxazole, one doublestrength tablet PO bid, is useful in cases of
CA-MRSA since 95% of community-acquired
MRSA strains are susceptible to it invitro. Other
agents that can be used for CA-MRSA include:
1. Clindamycin: 300 to 450 mg q6-8h also
inhibits toxin production. If strain tests
sensitive to clindamycin but resistant to
erythromycin, then a D test must be

done to ensure there will not be inducible resistance while on therapy with the
clindamycin.
2. Doxycycline: 100 mg PO q12h and minocycline also have some activity against
MRSA.
3. Rifampin: never used alone but can be
used with one of the other oral agents


Vancomycin 15-20 mg/kg IV q8 to 12h
is the mainstay of parenteral therapy for
MRSA infections. There is an increasing concern of MRSA strains developing tolerance
to vancomycin, requiring higher doses to
achieve eradication. True vancomycin resistant strains (MIC 32 mg/L) remain rare.
Vancomycin trough levels of at least 15 to
20 mcg/ml are recommended to treat MRSA
infections.
Linezolid 600 mg PO or IV bid is a synthetic
oxazolidinone FDA-approved for MRSA skin
and soft tissue infections and pneumonia. It
has been shown to be more effective than
vancomycin for MRSA pneumonia. However,
its cost is more than 10 times as much as
vancomycin.
Daptomycin: 4 mg/kg/day to 6 mg/kg/day
IV is approved for skin and soft tissue infections, bacteremia and right-sided endocarditis but should not be used for pneumonia as
it is inactivated by pulmonary surfactant.
Tigecycline: 100 mg IV load, then 50 mg IV
q12h, is approved for MRSA skin and soft
tissue infections and intraabdominal abscess.
Ceftaroline is a fifth-generation cephalosporin, also effective against MRSA but only skin
and soft tissue infections, not pneumonia:
600 mg IV q12h.

CHRONIC Rx
Patients with MRSA colonization may have
reexposure or may be unable to eradicate
colonized state.
Oral agents used to attempt eradication of
colonization are rifampin, tetracycline, and
minocycline.
COMPLEMENTARY &
ALTERNATIVE MEDICINE
Mupirocin ointment may be administered to
the nares to attempt to decolonize; it can also
be applied to infected skin sites.
Chlorhexidine 2% or 4% wash may be used
to lower skin burden of colonization.

EVIDENCE
Available at www.expertconsult.com

SUGGESTED READINGS
Available at www.expertconsult.com
AUTHOR: GLENN G. FORT, M.D., M.P.H.

Diseases
and Disorders

DEFINITION
Methicillin-resistant Staphylococcus aureus
(MRSA) is a common bacterial pathogen with
resistance to many antibiotics. It is defined as a
S. aureus that shows a minimum inhibitory concentration (MIC) of greater than or equal to 4 mcg/
ml to oxacillin. There are now two types of MRSA:
HA-MRSA: hospital-acquired MRSA, usually
multidrug resistant


CA-MRSA: community-acquired MRSA; an
emerging pathogen, usually acquired outside
of the hospital setting; resistance may differ
from HA-MRSA and is generally susceptible
to more antibiotics than HA-MRSA

ETIOLOGY
CA-MRSA: the most prevalent strain in the US
on pulse field electrophoresis (PFGE) is called
USA 300
1. CA-MRSA: common cause of skin and soft
tissue infections in the emergency room.
It can, however, also cause necrotizing
pneumonia, sepsis, osteomyelitis, etc.
2. Virulence factors particular to CA-MRSA:
Panton-Valentine leukocidin (PVL) toxin,
alpha-hemolysin toxin, phenol soluble
modulins, etc., that enhance ability to
cause infection
HA-MRSA: most strains on PFGE are USA 100
or USA 200 and tend to have multidrug resistance. Patients with HA-MRSA infection have
higher mortality and morbidity than patients
with a methicillin-sensitive S. aureus (MSSA)
infection.

797

Methicillin-Resistant Staphylococcus aureus (MRSA)


EVIDENCE
Abstract[1]
Background:
Telavancin is a lipoglycopeptide bactericidal against gram-positive
pathogens.
Methods:
Two methodologically identical, double-blind studies (0015 and 0019)
were conducted involving patients with hospital-acquired pneumonia
(HAP) due to gram-positive pathogens, particularly methicillin-resistant
Staphylococcus aureus (MRSA). Patients were randomized 1:1 to telavancin (10 mg/kg every 24 h) or vancomycin (1 g every 12 h) for 721
days. The primary end point was clinical response at follow-up/test-ofcure visit.
Results:
A total of 1503 patients were randomized and received study medication (the all-treated population). In the pooled all-treated population, cure
rates with telavancin versus vancomycin were 58.9% versus 59.5%
(95% confidence interval [CI] for the difference, 5.6% to 4.3%). In the
pooled clinically evaluable population (n = 654), cure rates were 82.4%
with telavancin and 80.7% with vancomycin (95% CI for the difference,
4.3% to 7.7%). Treatment with telavancin achieved higher cure rates
in patients with monomicrobial S. aureus infection and comparable cure
rates in patients with MRSA infection; in patients with mixed gram-positive/gram-negative infections, cure rates were higher in the vancomycin
group. Incidence and types of adverse events were comparable between
the treatment groups. Mortality rates for telavancin-treated versus
vancomycin-treated patients were 21.5% versus 16.6% (95% CI for the
difference, 0.7% to 10.6%) for study 0015 and 18.5% versus 20.6%
(95% CI for the difference, 7.8% to 3.5%) for study 0019. Increases in
serum creatinine level were more common in the telavancin group (16%
vs 10%).
Conclusions:
The primary end point of the studies was met, indicating that telavancin
is noninferior to vancomycin on the basis of clinical response in the treatment of HAP due to gram-positive pathogens.
Abstract[2]
Background:
Methicillin-resistant Staphylococcus aureus (MRSA) is an important
cause of nosocomial pneumonia. Societal guidelines suggest linezolid
may be the preferred treatment of MRSA nosocomial pneumonia. We
investigated the efficacy of linezolid compared with glycopeptide antibiotics (vancomycin or teicoplanin) for nosocomial pneumonia.
Methods:
This was a systematic review and meta-analysis of English language,
randomized, controlled trials comparing linezolid to glycopeptide antibiotics for suspected MRSA pneumonia in subjects >12 years of age. A
highly sensitive search of PubMed MEDLINE and Cochrane Central Register of Controlled Trials databases identified relevant studies.

Results:
Eight trials encompassing 1,641 subjects met entry criteria. Linezolid
was not superior to glycopeptide antibiotics for end points of clinical success (relative risk [RR] linezolid vs glycopeptide, 1.04; 95% CI, 0.971.11; P = .28), microbiologic success (RR, 1.13; 95% CI, 0.97-1.31; P =
.12), or mortality (RR, 0.91; 95% CI, 0.69-1.18; P = .47). In addition, clinical success in the subgroup of subjects with MRSA-positive respiratory
tract culture (RR, 1.23; 95% CI, 0.97-1.57; P = .09) was not significantly
different from those without MRSA (RR, 0.95; 95% CI, 0.83-1.09; P =
.48), P for interaction, 0.07. The risk for adverse events was not different between the two antibiotic classes (RR, 0.96; 95% CI, 0.86-1.07;
P = .48).
Conclusion:
Randomized controlled trials do not support superiority of linezolid over
glycopeptide antibiotics for the treatment of nosocomial pneumonia. We
recommend that decisions between linezolid or glycopeptide antibiotics
for empirical or MRSA-directed therapy of nosocomial pneumonia depend on local availability, antibiotic resistance patterns, preferred routes
of delivery, and cost, rather than presumed differences in efficacy.

Evidence-Based References
Rubinstein E: for the ATTAIN Study Group. Telavancin versus vancomycin for
hospital-acquired pneumonia due to gram-positive pathogens, Clin Infect Dis
52:3140, 2011.
Walkey A etal.: Linezolid vs glycopeptide antibiotics for the treatment of
suspected methicillin-resistant nosocomial pneumonia: a meta-analysis of
randomized controlled trials, Chest 139:11481155, 2011.

SUGGESTED READINGS
Gould IM etal.: New insights into methicillin-resistant Staphylococcus aureus
(MRSA) pathogenesis, treatment and resistance, Int J Antimicrob Agents
39(2):96104, 2012.
Holland TL etal.: Clinical management of Staphylococcus aureus bacteremia, a
review, JAMA 312(13):13301341, 2014.
Liv C etal.: Clinical practice guidelines by the Infectious Diseases Society of
America for the treatment of methicillin resistant Staphylococcus aureus infections in adults and children, Clin Infect Dis 52:285292, 2011.
McConeghy K etal.: Agents for the decolonization of methicillin resistant.
Staphylococcus aureus, Pharmacotherapy 29:263280, 2009.
Wunderink RG etal.: Linezolid in methicillin-resistant Staphylococcus aureus
nosocomial pneumonia: a randomized, controlled study, Clin Infect Dis
54:621629, 2012.

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